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Analysis of drug-drug interactions in patients admitted to hospital (II.)
Mašková, Daniela ; Vlček, Jiří (advisor) ; Malý, Josef (referee)
Candidate: Daniela Mašková1 Supervisor: prof. RNDr. Jiří Vlček, CSc.1 Consultant: PharmDr. Zuzana Očovská1 Title of the master thesis: Analysis of drug-drug interactions in patients admitted to hospital (II.) 1 Department Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Králové, Charles University Drug-drug interactions (DDIs) are part of drug-related problems. Drug-related problems can be either potential (possibly leading to real problems for the patient) or manifest (the problem already impacts the patient). This study aims to identify potential DDIs in the medication history of patients acutely admitted to University Hospital Hradec Králové via the department of emergency medicine. The objectives are to determine the prevalence of hospital admissions with at least one potential DDI in the medication history and characterize the identified potential DDIs with respect to their mechanism, severity rating, level of documentation, and potential consequences. Another objectives was to identify medication classes involved in potential DDI. The design of this study is an observational cross-sectional study. The data were obtained from the previous study examining the drug-relatedness of 1252 hospital admissions. For the purpose of my master's thesis, a sample of 378 hospital admissions was...
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Effect of the anticancer drug cabozantinib on cytochrome P450 activity
Slobodníková, Eva ; Dračínská, Helena (advisor) ; Václavíková, Radka (referee)
Cabozantinib is an anti-cancer drug used mainly for the treatment of thyroid and renal cell carcinoma. It is classified as a low molecular weight selective tyrosine kinase inhibitor. Tyrosine kinases play a key role in signal transduction and regulation of many cellular processes such as growth, differentiation, and proliferation. The changes in the tyrosine kinase pathways are associated with the formation and progression of tumors where their growth is uncontrolled. Tyrosine kinase inhibitors act on tyrosine kinase receptors, thereby preventing the spread of cancer cells and slowing down the progression of cancer. Because cabozantinib, like other clinically used drugs, is metabolized by cytochromes P450, adverse drug interactions may occur that result in altered pharmacokinetics of the administered drugs and a consequent decrease in the efficacy of these drugs. In this diploma thesis, the effect of cabozantinib on the activity of the main enzymes of phase I biotransformation of xenobiotics, cytochromes P450, was investigated in vitro. The effect on the activity of both rat and human cytochrome P450 isoforms involved in xenobiotic metabolism was studied. CYP isoforms were predominantly incubated with cabozantinib at two concentrations; 10 µM and a concentration corresponding to the substrate...
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Methods for Predicting Drug Side Effects in Silico
Cicková, Pavlína ; Lexa,, Matej (referee) ; Berka,, Karel (referee) ; Provazník, Ivo (advisor)
Vývoj a výzkum léčiv je oblastí současné vědy, jejíž nedílnou součástí je i využití výpočetních metod. Z důvodu nákladnosti a časové náročnosti laboratorních přístupů, metody in silico sehrávají svou významnou roli. I přes rychlý vývoj výpočetních technik využívaných při vývoji léků, však není drtivá většina zkoumaných molekul v procesu vývoje úspěšná a do schvalovací fáze nepostoupí. Nejen proto se nejmodernější strategie návrhu potenciálních nových léčiv zaměřují na opětovné zkoumání již schválených léků a berou do úvahy i analýzu podobností. Tato práce popisuje vývoj a aplikaci souboru několika workflow, jež byl vytvořen v rámci analytické platformy KNIME a jež implementuje metody strojového učení za účelem predikce nežádoucích účinků léčiv. Součástí prezentovaných workflow je získání dat, jejich předzpracování, výpočet metrik podobností a provedení explorační analýzy. Následně je využito klasifikačních modelů k predikci specifických nežádoucích účinků léčiv. Tato predikce vychází z principů technik založených na podobnosti. K natrénování modelů rozhodovacích stromů pro predikci potenciální asociace nežádoucích účinků s léčivy byly využity strukturní a jiné podobnosti schválených molekul léčiv. Hlavní přínos práce spočívá především v přenositelnosti použitých metod. Soubor workflow je určen k využití jako vhodný nástroj k řešení výzkumných otázek ohledně podobnosti léčiv a jelikož analytická platforma KNIME poskytuje uživatelsky přívětivé grafické rozhraní, není nutné, aby měli uživatelé pokročilé zkušenosti v oblasti strojového učení nebo programování, aby mohli soubor navržených workflow v rámci této platformy pro své analýzy využít.
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Analysis of drug-drug interactions in patients admitted to hospital (II.)
Mašková, Daniela ; Vlček, Jiří (advisor) ; Malý, Josef (referee)
Candidate: Daniela Mašková1 Supervisor: prof. RNDr. Jiří Vlček, CSc.1 Consultant: PharmDr. Zuzana Očovská1 Title of the master thesis: Analysis of drug-drug interactions in patients admitted to hospital (II.) 1 Department Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Králové, Charles University Drug-drug interactions (DDIs) are part of drug-related problems. Drug-related problems can be either potential (possibly leading to real problems for the patient) or manifest (the problem already impacts the patient). This study aims to identify potential DDIs in the medication history of patients acutely admitted to University Hospital Hradec Králové via the department of emergency medicine. The objectives are to determine the prevalence of hospital admissions with at least one potential DDI in the medication history and characterize the identified potential DDIs with respect to their mechanism, severity rating, level of documentation, and potential consequences. Another objectives was to identify medication classes involved in potential DDI. The design of this study is an observational cross-sectional study. The data were obtained from the previous study examining the drug-relatedness of 1252 hospital admissions. For the purpose of my master's thesis, a sample of 378 hospital admissions was...
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Interaction of drugs used in gynecology and urology and their management
Kupka, Vojtěch ; Doseděl, Martin (advisor) ; Kostřiba, Jan (referee)
Interaction of drugs used in gynecology and urology and their management Author: Kupka Vojtěch Tutor: PharmDr. Martin Doseděl Ph.D., Department of Social and Clinical Pharmacy, Charles University in Prague, Faculty of Pharmacy in Hradec Králové Introduction: Drug interactions represent a serious health problem and they cause adverse drug effects and toxicity of drugs. Objectives: The goal of the thesis was to create an overview of possible drug interactions with drugs used in gynecological and urological practice. Methodology: From a theroretical introduction was selected registred drugs to 1 st January 2015 by State Institute for Drug Controle. Information about drug interactions were collected and collated from databases Vademecum Infopharm and Micromedex. From database Micromedex, the drug interactions were selected with quality of documentation "excellent" or "good". Pubmed database (www.pubmed.gov) with entering key words "basic drug", "drug interaction" and "interactive drug" was applied to create a current information. To complement the information was also gathered from magazines Practical Pharmacy and Clinical Pharmacology and Pharmacy. In case of not finding relevant information was drawn from the summary information of medicine (SPC). Results: The results were categorized into a research...
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Polymorphism of drug metabolizing enzymes as a potential target of prevention of serious treatment complications in neonates and infants
Hronová, Karolína ; Slanař, Ondřej (advisor) ; Paluch, Zoltán (referee) ; Hladík, Michal (referee)
Univerzita Karlova 1. lékařská fakulta Studijní program: Biomedicína Studijní obor: Preventivní medicína MUDr. Karolína Hronová Polymorfismus genů účastnících se v metabolismu léčiv jako potenciální cíl prevence závažných komplikací léčby u novorozenců a dětí Polymorphism of drug metabolizing enzymes as a potential target of prevention of serious treatment complications in neonates and infants Disertační práce- ABSTRAKT V ANGLICKÉM JAZYCE Školitel: prof. MUDr. Ondřej Slanař, Ph.D. Konzultant: MUDr. Pavla Pokorná, PhD. Praha, 2018 Abstract Background and aims: The safety of analgosedative drugs includes drug interactions, adverse effects, withdrawal syndrome and drug dependence are factors that significantly affect morbidity and mortality. Its prevention is critical for quality improvement of care in paediatric patients. The aim of the thesis was to evaluate the prediction of efficacy and safety of analgosedative drugs sufentanil, midazolam, tramadol and valproic acid in neonates and children based on the occurrence of selected pharmacogenetic biomarkers. The incidence of drug interactions of phenobarbital with other analgosedative drugs has also been evaluated. Methodology: The thesis is based on two studies conducted on Intensive and Resuscitation Care Unit of the Clinic of Paediatric and Adolescent...
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Drug interactions of cardiovascular drugs and their analysis in the patients of community pharmacy II.
Skořepová, Lenka ; Malý, Josef (advisor) ; Babica, Jan (referee)
Drug interactions of cardiovascular drugs and their analysis in the patients of community pharmacy II. Author: Lenka Skořepová1 Tutor: PharmDr. Josef Malý, Ph.D.1 1 Department of Social and Clinical Pharmacy, Charles university in Prague, Faculty of Pharmacy in Hradec Králové Introduction: Drug interactions are a major cause of toxicity, side effects of drugs and increase the risk of harm to the patient. The pharmacist has an indispensable role in the process of minimizing risks and resolving of drug interactions. Objectives: The aim of the thesis was to carry out a research focused on drug interactions of selected groups of cardiovascular drugs and to describe their management in clinical practice, which could be used during dispensing medicine. Then was evaluated occurrence of these drug interactions in pharmacotherapy of community pharmacy patients. Methods: With the help of selected databases were described individual drug interactions of ACEI and created their management in clinical practice. Sample of patients of community pharmacy was screened for drug interactions. The data were processed by retrospective analysis. For 12 patients with drug interactions were processed case reports and tested solution of drug interactions with using of described management of drug interactions during the...
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In vitro and ex vivo study of drug-drug interactions of antivirals on intestinal membrane transporters
Halodová, Veronika ; Červený, Lukáš (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Veronika Halodová Supervisor: doc. PharmDr. Lukáš Červený, Ph.D. Title of diploma thesis: In vitro and ex vivo study of drug-drug interactions of antivirals on intestinal membrane transporters Tenofovir (TFV) is the first-line agent in the treatment of hepatitis B virus (HBV) infection for patients aged over 12 years and one of the first-line choices for the combination antiretroviral therapy (cART) of infections caused by human immunodeficiency virus (HIV). Two commercially available prodrugs have been developed for oral administration of TFV, tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide fumarate (TAF). These prodrugs increase TFV membrane permeability and oral bioavailability. One of the factors that can affect the bioavailability of orally administrated drugs is active transport mediated by efflux transporters, mainly by P-glycoprotein (ABCB1, P-gp) and Breast cancer resistance protein (ABCG2, BCRP). It has been already proved that TDF and TAF are substrates of both of these transporters. The goal of this diploma thesis was to use in vitro and ex vivo models of intestinal barrier to assess the impact of the efflux transporters on TDF and TAF transport in the intestine and on their...
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Novel bile acid derivatives as a promising therapeutic approach for liver and metabolic disorders
Štefela, Alžbeta ; Pávek, Petr (advisor) ; Vítek, Libor (referee) ; Juřica, Jan (referee)
IN ENGLISH LANGUAGE Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmacology and Toxicology Candidate: Mgr. Alžbeta Štefela Supervisor: Prof. PharmDr. Petr Pávek, PhD. Title of the doctoral thesis: Novel bile acid derivatives as promising therapeutic approach Bile acids (BAs) are amphipathic steroidal molecules that are traditionally known to facilitate intestinal digestion and absorption of lipids and fat-soluble substances. On top, the recent findings have revealed that they represent important signaling agents involved in the orchestration of lipid, glucose and energy metabolism and immune response. BAs exhibit these roles by activating intracellular nuclear receptors such as farnesoid X (FXR), pregnane X (PXR) vitamin D receptors. Furthermore, BAs act as endocrine signaling molecules and activate numerous biological cascades via a membrane G-protein-coupled receptor, termed TGR5. Therefore, the extensive modulation of BA scaffold underwent to identify compounds with specific targeting of above-mentioned receptors as a promising therapeutic approach for the treatment of various liver and metabolic disorders including cholestasis, biliary cirrhosis, nonalcoholic steatohepatitis or diabetes. The principal aim of this doctoral thesis was to investigate the structure...
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Drug Information Centre service analysis IV. - drug interactions
Michálek, Georg ; Malá, Kateřina (advisor) ; Doseděl, Martin (referee)
Drug Information Centre service analysis IV. - drug interactions Author: Georg Michálek Supervisor: PharmDr. Kateřina Malá, Ph.D. Consultant: PharmDr. Petra Rozsívalová Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic Introduction: Drug information centre (DIC) of the Faculty of Pharmacy in Hradec Králové, Charles University, and University Hospital Hradec Králové was established in 1994. It provides drug information to healthcare professionals in the form of timely and accurate answers to drug-related enquiries, including drug interactions (DI). Aim: This study aimed to analyse enquiries related to DI processed by DIC from 2015 to 2020 and to solve three drug enquiries related to drug interactions. Methods: Quantitative and qualitative analysis of drug enquiries was carried out. Data was collected from individual enquiries related, but not limited to drug-drug, drug-herbal, and drug-disease interactions. The quantitative analysis based on descriptive statistical methods was performed on two levels: enquiry level and drug interaction level. On the enquiry level, ATC codes found in the enquiries were analysed and on the drug interaction level various parameters assigned to each DI were analysed, such as interacting components,...
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